Pushing the Boundaries of Knowledge in Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder caused by mutations in the SERPINA1 gene. AATD is one of the leading causes of emphysema in young adults and of liver cirrhosis in children and adults. Despite significant underdiagnosis and high clinical variability, recent research is rapidly transforming the field. Advances in molecular biology and translational medicine have identified new biomarkers and therapeutic targets, although reliable predictors of disease progression remain limited. While augmentation therapy is the only approved pharmacological option for pulmonary involvement and no specific treatment exists for liver disease, innovative strategies are remodeling the therapeutic landscape. Gene therapy, RNA interference, gene editing, and epigenetic modulation are showing promising preclinical and early clinical results, aiming to correct the underlying defect rather than manage symptoms. This review focuses on these emerging advances, highlighting cutting-edge preclinical and translational developments with potential to redefine AATD management and move toward curative approaches.